4-aminoethoxy indoles

Compounds of the formula: ##STR1## in which R.sub.1 is hydrogen, alkyl, cycloalkylalkyl, arylalkyl, (haloaryl)alkyl, (alkoxyaryl)alkyl, thienylmethyl, furanylmethyl, pyridinylmethyl, alkylphenyl, 4-fluorobutyrophenone or 6-fluoro-1,2-benzisoxazol-yl-propyl; X is hydrogen, halogen, cyano, alkyl, acetyl, trifluoroacetyl, trifluoromethyl or formyl; Y is hydrogen, halogen, alkoxy or alkyl; or a pharmaceutically acceptable salt thereof are inhibitors of dopamine synthesis and release, useful in the treatment of schizophrenia, Parkinson's Disease, Tourette's Syndrome, alcohol addiction, cocaine addiction, and addiction to analagous drugs and they also have affinity for the 5-HT.sub.1A receptors which characterizes them as useful in the treatment of diseases attending disturbances in the serotinergic systems, such as anxiety, stress, depression, sexual dysfunctions and sleep disturbances.

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Claims

1. A compound of formula I ##STR5## in which: R.sub.1 is alkyl of 1 to 10 carbon atoms, monocyclic cycloalkylalkyl of 6 to 12 carbon atoms, arylalkyl of 7 to 12 carbon atoms, (haloaryl)alkyl of 7 to 12 carbon atoms, (alkoxyaryl)alkyl of 8 to 12 carbon atoms, alkylphenyl of 7 to 12 carbon atoms, or 4-fluorobutyrophenone;

X is hydrogen, halogen, cyano, alkyl of 1 to 6 carbon atoms, acetyl, trifluoroacetyl, trifluoromethyl or formyl;
Y is hydrogen, halogen, alkoxy of 1 to 6 carbon atoms or alkyl of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 in which:

R.sub.1 is alkyl of 1 to 10 carbon atoms, cyclohexylmethyl, arylalkyl of 7 to 12 carbon atoms, (haloaryl)alkyl of 7 to 12 carbon atoms or (alkoxyaryl)alkyl of 8 to 12 carbon atoms;
X is H, halogen, cyano, alkyl of 1 to 6 carbon atoms, acetyl, trifluoroacetyl, trifluoromethyl or formyl;
Y is hydrogen, halogen, alkoxy of 1 to 6 carbon atoms or alkyl of 1 to 6 carbon atoms;

3. A compound of claim 1 in which R.sub.1 is alkyl of 1 to 6 carbon atoms, benzyl, halobenzyl, alkoxybenzyl of 8 to 12 carbon atoms or alkylbenzyl of 8 to 12 carbon atoms; X is hydrogen, halogen or trifluoroacetyl and Y is hydrogen or halogen; or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition of matter comprising a compound of the formula: ##STR6## in which: R.sub.1 is alkyl of 1 to 10 carbon atoms, monocyclic cycloalkylalkyl of 6 to 12 carbon atoms, arylalkyl of 7 to 12 carbon atoms, (haloaryl)alkyl of 7 to 12 carbon atoms, (alkoxyaryl)alkyl of 8 to 12 carbon atoms, alkylphenyl of 7 to 12 carbon atoms, or 4-fluorobutyrophenone;

X is hydrogen, halogen, cyano, alkyl of 1 to 6 carbon atoms, acetyl, trifluoroacetyl, trifluoromethyl or formyl;
Y is hydrogen, halogen, alkoxy of 1 to 6 carbon atoms or alkyl of 1 to 6 carbon atoms;

14. A method for reducing dopamine synthesis and release in a patient suffering from hyperactivity of the dopaminergic systems, which comprises administering to said patient a compound of the formula: ##STR7## in which: R.sub.1 is alkyl of 1 to 10 carbon atoms, monocyclic cycloalkylalkyl of 6 to 12 carbon atoms, arylalkyl of 7 to 12 carbon atoms, (haloaryl)alkyl of 7 to 12 carbon atoms, (alkoxyaryl)alkyl of 8 to 12 carbon atoms, alkylphenyl of 7 to 12 carbon atoms, or 4-fluorobutyrophenone;

X is hydrogen, halogen, cyano, alkyl of 1 to 6 carbon atoms, acetyl, trifluoroacetyl, trifluoromethyl or formyl;
Y is hydrogen, halogen, alkoxy of 1 to 6 carbon atoms or alkyl of 1 to 6 carbon atoms;

15. A method for treating schizophrenia which comprises administering to a patient suffering from schizophrenia, orally or parenterally, a compound of the formula: ##STR8## in which: R.sub.1 is alkyl of 1 to 10 carbon atoms, monocyclic cycloalkylalkyl of 6 to 12 carbon atoms, arylalkyl of 7 to 12 carbon atoms, (haloaryl)alkyl of 7 to 12 carbon atoms, (alkoxyaryl)alkyl of 8 to 12 carbon atoms, alkylphenyl of 7 to 12 carbon atoms, or 4-fluorobutyrophenone;

X is hydrogen, halogen, cyano, alkyl of 1 to 6 carbon atoms, acetyl, trifluoroacetyl, trifluoromethyl or formyl;
Y is hydrogen, halogen, alkoxy of 1 to 6 carbon atoms or alkyl of 1 to 6 carbon atoms;
Referenced Cited
U.S. Patent Documents
3904645 September 1975 McManus
3906000 September 1975 McManus
5013761 May 7, 1991 Beedle et al.
5541199 July 30, 1996 Mewshaw
5552429 September 3, 1996 Wong et al.
5627196 May 6, 1997 Audia et al.
Foreign Patent Documents
25558 January 1966 FRX
Other references
  • Corsini et al., Adv. Biochem. Psychopharmacol 16, 645-648 (1977). Tamminga et al. Science, 200, 567-568 (1978). Tamminga et al., Arch. Gen. Psychiatry, 43, 398-402 (1986). Lahti et al., Mol. Pharma. 42, 432-438 (1993). Hosohata et al., "A non-selective beta-blocker, bopindolol, exhibits high affinity to 5-HT1A receptor subtype in rat brain as assayed by competition binding experiments", Biogenic Amines, vol. 12, No. 3. pp. 253-258, 1996.
Patent History
Patent number: 5958965
Type: Grant
Filed: Aug 12, 1997
Date of Patent: Sep 28, 1999
Assignee: American Home Products Corporation (Madison, NJ)
Inventors: Richard Eric Mewshaw (Princeton, NJ), Michael Byron Webb (Levittown, PA)
Primary Examiner: Dwayne C. Jones
Attorney: Rebecca R. Barrett
Application Number: 8/909,803